Curcumin Mitigates TNFα-Induced Caco-2 Cell Monolayer Permeabilization Through Modulation of NF-κB, ERK1/2, and JNK Pathways

Scope This work studies the capacity of curcumin to inhibit tumor necrosis alpha (TNF alpha)-induced inflammation, oxidative stress, and loss of intestinal barrier integrity, characterizing the underlying mechanisms. Methods and Results Caco-2 cell monolayers are incubated with TNF alpha (10 ng mL(-1)), in the absence or presence of curcumin. TNF alpha causes an increase in interleukin (IL)-6 and IL-8 release, which is inhibited by curcumin in a dose-dependent manner (half-maximal inhibitory concentration (IC50) = 3.4 mu M for IL-6). Moreover, TNF alpha leads to: i) increased intercellular adhesion molecule 1 (ICAM-1) and NLRP3 inflammasome expression; ii) increased cell monolayer permeability and decreased levels of tight junction proteins; iii) increased cellular and mitochondrial oxidant production; iv) decreased mitochondrial membrane potential and complex I-III activity; v) activation of redox-sensitive pathways, i.e., nuclear factor-kappa B (NF-kappa B), extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinases (JNK); and vi) increased myosin light-chain kinase (MLCK) expression and phosphorylation levels of myosin light-chain protein MLC. Curcumin (2-8 mu M) inhibits all these TNF alpha-triggered undesirable outcomes, mostly showing dose-dependent effects. Conclusion The inhibition of NF-kappa B, ERK1/2, and JNK activation could be in part involved in the capacity of curcumin to mitigate intestinal inflammation, oxidant production, activation of redox-sensitive pathways, and prevention of monolayer permeabilization. These results support an action of dietary curcumin in sustaining gastrointestinal tract physiology.

Automated summary

This study investigates the effects of curcumin in inhibiting inflammation, oxidative stress, and loss of intestinal barrier integrity induced by TNF alpha. The results suggest that curcumin can mitigate these undesired outcomes by inhibiting the activation of NF-kB, ERK1/2, and JNK pathways.